The purpose of this proposal (responding to RFA EB-005-001) is to pursue the integrated development of a functional brain imaging approach based on the fast optical signal. This signal is characterized by rapid changes in cortical transparency occurring immediately after stimulation and simultaneous with electrophysiological measures of neuronal activity. The current proposal unites three groups (at the University of Illinois at Urbana-Champaign - UIUC, University of California-Irvine - UCI, and Pennsylvania State University - PSU) that have played a critical role in the discovery and initial observations of the fast optical signal in humans. The main goals of the proposed research, covering five of the six goals stated in the RFA, are: (a) To investigate the biophysical phenomena underlying the fast optical signals through a combination of simulation studies and measurements conducted on animal models, comparing fast optical signals and electrophysiological measures of neuronal activity. (RFA GOALS#1&2) (b) To examine the relationship between intracranial changes and optical parameters recorded at the scalp and used for detecting the fast optical signals in humans. This will involve recording of fast optical signals in humans as well as Monte Carlo simulation. (RFA GOALS#4&6). (c) To develop and validate mapping and other analytic tools for the 3-D reconstruction of cortical activity based on realistic head models, through the comparison of optical and fMRI data (RFA GOAL#5). (d) To significantly improve the signal-to-noise ratio (S/N) of optical signals through radical modifications of the current instrumental designs and improvements in recording and filtering methods. (RFA GOAL#6).